Donor-specific HLA alloantibodies: long-term impact on cardiac allograft vasculopathy and mortality after heart transplant.
OBJECTIVE
The clinical significance of anti-HLA-alloantibodies remains controversial. Recent studies have linked development of donor-specific HLA-antibodies to chronic allograft rejection and graft loss after heart, kidney, and lung transplants. We investigated the clinical impact of donor-specific humoral alloreactivity during the follow-up of heart transplant recipients.


METHODS
The sera of 213 heart transplant recipients were screened by enzyme-linked immunosorbent assay for HLA-antibody production. The antigen specificity of the detected HLA class I and class II antibodies was identified using a Luminex assay. Outcome variables were survival, cardiac allograft vasculopathy, and cellular rejection.


RESULTS
The cumulative incidence of alloantibody formation was 23/213 patients (10.8%). The majority of detected alloantibodies were donor-specific for HLA class II. Mean follow-up at antibody measurements was 7 -/+ 4.9 years. Freedom from vasculopathy at 5 and 10 years was 77.9% and 26% in donor-specific HLA-antibody-positive patients compared with 84.6% and 65.2% in antibody-negative controls (P = .025). Freedom from treated, biopsy-proven rejection was 44.4% for donor-specific HLA-antibody-positive patients compared with 70.2% in the controls (P = .06). Multivariate analyses identified donor-specific HLA antibody positivity as an independent risk factor for vasculopathy.


CONCLUSIONS
Our results demonstrate a strong correlation between the development of donor-specific HLA antibodies and adverse outcomes after heart transplant. Detection of donor-specific HLA antibodies might identify high-risk patients and offer an opportunity for early clinical intervention and modification of immunosuppression.
Kaczmarek
Ingo
I
Department of Cardiac Surgery, University Hospital Grosshadern, Ludwig-Maximilians-University, Marchioninistrasse 15, 81377 Munich, Germany. Ingo.Kaczmarek@med.uni-muenchen.de
Deutsch
Marcus-Andre
MA
Kauke
Teresa
T
Beiras-Fernandez
Andres
A
Schmoeckel
Michael
M
Vicol
Calin
C
Sodian
Ralf
R
Reichart
Bruno
B
Spannagl
Michael
M
Ueberfuhr
Peter
P
D000328:Adult; D000917:Antibody Formation; D002311:Cardiomyopathy, Dilated / Q000601:surgery; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000453:epidemiology / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology* / Q000401:mortality; D006801:Humans; D007518:Isoantibodies / Q000097:blood*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016019:Survival Analysis; D017741:Survivors; D013997:Time Factors; D014019:Tissue Donors
D006680:HLA Antigens; D007518:Isoantibodies